This invention relates to a process for the preparation of certain thieno-imidazole derivatives including descarboxybiotin. More particularly the invention is concerned with a process for the preparation of descarboxybiotin and a process for the preparation of descarboxythiobiotin. Both descarboxybiotin and descarboxythiobiotin are useful intermediates for the preparation of biotin.
Biotin is a water-soluble vitamin required by higher animals and by many microorganisms. Biosynthesis of biotin by selected yeasts, molds and bacteria is well known. U.S. Pat. No. 3,393,129 discloses the use of a d-biotin-producing strain of bacterium of the genus Sporobolomyces for commercial production of this vitamin. Chemical synthesis is reported in U.S. Pat. Nos. 2,489,235; 2,489,236; 4,029,647 and 4,124,595.
As industrial demand for d-biotin increases, the search for improved synthetic processes continues.
U.S. Pat. No. 4,468,516 discloses a process for the preparation of biotin and certain intermediates useful in such process. Among said intermediates is descarboxybiotin, i.e. the compound hexahydro-2-oxo-4-pentyl-1-H-thieno(3,4-d)-imidazole, of the formula: ##STR1## and descarboxythiobiotin, i.e. the compound hexahydro-2-thioxo-4-pentyl-1-H-thieno(3,4-d)imidazole, of the formula: ##STR2##
According to the disclosure in U.S. Pat. No. 4,468,516 descarboxybiotin may be prepared by reacting descarboxythiobiotin with a haloalcohol, preferably bromoethanol, in an polar solvent such as ethanol, methoxyethanol or diglyme, and refluxing under an inert gas, preferably nitrogen, until reaction is essentially complete, from 2 to 24 hours, and then treating with a weak base, for example, an alkali metal carbonate, preferably a saturated solution of sodium carbonate.
U.S. Pat. No. 4,468,516 also discloses that the descarboxythiobiotin itself may be prepared by reacting an intermediate alcohol, i.e. tetrahydro-3,3-pentamethylene-7-hydroxymethyl-5-thioxo-1-pentyl-3H,5H-imid azo(1,5c)thiazole, of the formula: ##STR3## with trifluoroacetic acid.
It has now been found that descarboxybiotin and descarboxythiobiotin may be prepared by improved processes which are superior to the prior art processes for the reasons set out hereinafter. Additionally the processes are applicable to the preparation of other thieno-imidazole derivatives.